Acid-Base regulation II Flashcards
The effectiveness of respiratory compensation for metabolic acidosis is limited to several days at best. This is because lowering PCO2 has what effects?
Increases pH, reduces renal HCO3- reabsorption (which then lowers plasma HCO3-)
Net effect is as if no compensation has occurred at all
Predicted respiratory compensation for metabolic acidosis is a
1.5 mmHg drop in PCO2 per 1 meq/L decrease in HCO3-
Useful to determine whether or not appropriate respiratory compensation to metabolic acidosis has occurred versus the presence of a second (respiratory) based acid-base disorder
Winter’s Formula
Using Winter’s formula, if the calculated and measured PCO2 values are equal than we know that
Appropriate compensation is occuring
Using Winter’s formula, if the measured PCO2 is greater than the calculated PCO2, than we know there is either
Respiratory acidosis too or no compensation
Is a PCO2 of 40 mmHg in the presence of a metabolic acidosis normal?
NO
With a chronic metabolic acidosis, any PCO2 value significantly above what Winter’s predicts would indicate a
Co-existing respiratory acidosis
With a chronic metabolic acidosis, a measured PCO2 less than calculate by Winter’s formula reveals the presence of co-existing
Respiratory alkalosis
A normal pH with abnormal ABGs should immediately raise suspicion of a
Mixed acid-base disorder
The final compensatory mechanism for metabolic acidosis is via the
Renal acidification of urine
Assuming the kidneys are functioning normally, this process can begin within about 24 hours and is maximal at approximately
5-6 days
Renal compensation for metabolic acidosis predominantly involves enhanced elimination of
NH4+ (as NH4Cl)
As an example of the effectiveness of the kidneys in handling an increased acid load, a reduction of plasma HCO3- by only 4-5 meq/L can result in a
4-fold increase in NH4+ excretion over several days
Determined by calculating the difference between the predominant plasma cation (Na+) and the sum of the most abundant plasma anions (HCO3- and Cl-)
Anion gap (AG)
The normal range for AG is
7-16 meq/L
The AG is simply the difference between
Unmeasured cations - unmeasured anions
Accounts for the majority of unmeasured anions
Negative charges within proteins
Therefor, an increased gao can result from a fall in unmeasured cations, or (most often) an increase in
Unmeasured anions
An important unmeasured anion to note is
Albumin
In the case of hemoconcentration, where the concentration of albumin is increased, the anion gap would be
Elevated
In the event of hypoalbuminemia, for every 1g/dL drop in plasma albumin, AG should be adjusted downward by
2.5 meq/L
The accumulation of certain anions can occur during various types of
Metabolic acidoses
Elevated AG ALWAYS strongly suggests the presence of
Metabolic acidosis
Duringmetabolic acidosis, and in the absence of unmeasured anions, lost HCO3- is replaced in order to maintain electroneutrality. What replaces it?
Cl-
This normal anion gap metabolic acidosis is often referred to as
Hyperchloremic metabolic acidosis
Common with normal AG metabolic acidosis
Hyperchloremia
HCl + NaHCO3 → NaCl + H2CO3 → CO2 + H2O
In this example, what is the result of loss of NaHCO3 due to a GI pathology?
Metabolic acidosis from increase in HCL due to loss of NaHCO3-
HCl is buffered by remaining HCO3- which results in increased Cl-
Results is hyperchloremia with normal AG
However, if H+ were to combine with an unmeasured anion, than what would happen?
AG would be elevated
With this in mind, it is not unusual for plasma chloride to be lowered with an
AG metabolic acidosis
It is important to note that increased AG is not exclusive to metabolic acidosis and can occur during
Metabolic alkalosis
The main factors contributing to this are
- ) ECV depletion (contraction alkalosis) causing increased plasma [albumin]
- ) Increase lactate production
Can occur in compensation for alkalemia
Increased lactate production
Lactic acid, ketoacids, salicylic acid, oxalic acid, glycolic acid, and formic acid each carry negative charges, and will each induce an abnormal rise in
AG (causing metabolic acidosis)
ANother way to show the relationships between anionic acid accumulation and HCO3- loss
delta-delta difference
By convention, we set basal HCO3- to
24
By convention, we set the normal AG to be
12
What is the delta-delta difference?
dd = Measured AG + measured [HCO3-] - 36
If dAG - dHCO3- = 0 than there is a single acid-base disorder which is
Metabolic acidosis
If there is a 1:1 correlation between dAG and dHCO3-, i.e. dAG - dHCO3- = 0 +/- 5 than we have
Ketoacidosis
We have to calculate the dd difference in a different manner for
-due to the way lactate is cleared by the kidneys
Lactic acidosis
When we calculate dd diference during lactic acidosis, we know there is a SINGLE metabolic acid-base disorder if the value falls within
0 +/- 5
With the aforementioned in mind, dd values less than -5 warrant investigation for the presence of a
Mixed AG metabolic acidosis w/ non-AG metabolic acidosis
If dd is greater than 5, than we likely have a mixed
Metabolic acidosis with metabolic alkalosis
A mixed metabolic acidosis and metabolic alkalosis can occur during severe diabetic ketoacidosis where marked elevated ketones induce
Vomiting
Derived from pyruvic acid mostly from the processes of glycolysis or the deamination of alanine
Lactic acid (lactate + H+)
Lactic acid is buffered by HCO3- to yield lactate, which is subsequently metabolized into
Pyruvate
Pyruvate can then be further metabolized into
CO2 + H2O or glucose
Either metabolic pathway results in the generation of new
HCO3-
The catalysis of lactate requires its entry into the mitochondria and oxidative metabolism, processes which each require sufficient
O2
Thus, if O2 delivery is blocked, we can see the accumulation of
Lactic acid
Common causes are poor tissue perfusion leading to impaired oxidation and ischemia, such as what
results from cardiac arrest, shock, severe exercise, alcoholism, and many other pathologies
O2 delivery blockages that results in lactic acid buildup
During starvation, or perceived starvation, increased lipolysis results in an overabundance of
Free fatty acids delivered to the liver
Results in elevated serum glucagon and low serum insulin
Starvation
Caused by a lack of insulin or insulin resistance
Perceived starvation
In the face of this barrage, hepatic function resets leading to the preferential metabolism of FFA into
Ketoacids (rather than the preferred triglycerdies)
Signs of hyperglycemia with ketones in the urine correlate with
Diabetic ketoacidosis
Is measured as the difference between major urinary cations (Na+ and K+) and the major urinary anion (Cl-)
Urine AG
How do we calculate urine AG?
UAG = UNa + UK - UCl
Under normal conditions, urine AG will be at or very close to
Zero
Urine AG can be useful in discerning the cause of
Normal AG metabolic acidosis
Not useful with elevated AG acidosis
Urine AG
The most common cause of normal AG metabolic acidosis (due to GI loss of HCO3-)
Diarrhea
When pH drops, the kidneys will excrete H+ in the form of
NH4+
This so-called acidification of urine occurs in the distal portions of the structures known as
- Where urine is being formed
- Called distal acidification
Nephrons
Excreted with H+ in order to maintain electroneutrality
Cl-
Thus, if the kidneys are doing their job in response to metabolic acidosis, excreted urine will contain a lot of Cl- and this drives
Urine AG to negative values
A negative AG is usually in the range of
-20 to -50 meq/L
Acidoses that result from the inability of the kidneys to properly acidify urine
Renal Tubule Acidoses (RTA)
In an RTA, because H+ is not effectively cleared by the kidneys, the ratio of plasma HCO3-/H+ decreases and pH drops, thus forming a
Metabolic acidosis
Since these kidneys are sick, they can not excrete the excess H+, which means they will not excrete Cl- either, and this drives
Urine AG to positive values
An elevation in plasma [HCO3-] due to H+ loss
Metabolic alkalosis
Caused by diarrhea, antacid therapy, hypovolemia, vomiting, and nasogastric suction
Metbolic alkalosis
Contraction alkalosis around a set amount of HCO3-
-A concern with diuretic usage
Hypovolemia
The maintenance of metabolic alkalosis usually involves a defect in renal HCO3- secretion and excretion due to
Effective volume depletion and Cl- loss
Impeded due to excess HCO3-
Cl- resorption from the kidneys
The kidneys respond to volume depletion by increasing the reabsorption of
Na+
This process is mediated by
Aldosterone and An-II
In the context of volume depletion and metabolic alkalosis, An-II stimulates
Aldosterone secretion
An-II also acts with the kidneys to stimulate the
Proximal Na+/H+ exchanger and the Na+/HCO3- symporter
Remember that H+ secretion equates to
HCO3- reabsorption by the kidneys
Thus with elevated An-II, K+ secretion is upregulated (via aldosterone) and HCO3- reabsorption is
Directly enhanced
Signs of hypokalemia and hypochloremia often accompany
Metabolic alkalosis
To be more specific, to compensate for volume depletion, the kidneys attempt to increase the resorption of
Na+ and Cl-
It is important to understand that this process is coupled. In other words
There is a 1:1 ratio between Na+ resorption and Cl- resorption
With reduced Cl-, Na+ resorption can only occur at the expense of
K+ and H+ secretion
H+ secretion equates to increased HCO3- resorption and the alkalosis can be exacerbated by
K+ loss
In order to compensate for metabolic alkalosis, pH must be lowered , and this is accomplished via
-opposite of what is seen in metabolic acidosis
Decreased ventilation
In acid-base disturbances, we can see shifts between H+ and the most abundant intracellular cation
K+
There is a connection between metabolic alkalosis and
Hypokalemia
At the cellular level, increased extracellular pH (low [H+]) results in?
-The reason hypokalemia is associated with metabolic alkalosis
H+ translocating from cells to ECF. This is offset by K+ moving from ECF into cells. Thus ECF [K+] is decreased and we can see hypokalemia
How does hypokalemia result in metabolic alkalosis?
Low K+ causes K+ to move from cells to ECF. To maintain electroneutrality, H+ then moves from ECF into cells and the result is an increased pH
Abnormally increased K+ excretion may induce metabolic alkalosis, and hypokalemia actually promotes
Renal H+ secretion
The trade-off for H+ secretion is the generation and absorption of
HCO3-
Volume contraction, diminished glomerular filtration rate, and aldosterone excess often accompany
Metabolic alkalosis
Renal H+ secretion is stimulated by which three things?
- ) Aldosterone excess
- ) Hypovolemia
- ) Hypokalemia
How does acidosis result in hyperkalemia?
Acidosis impairs renal tubular K+ secretion and K+ excretion is diminished.
Increased extracellular H+ causes H+ to move into cells which results in K+ moving to the ECF to maintain electroneutrality
Hyperkalemia and acidosis are often coupled because hyperkalemia suppresses
H+ secretion from kidneys
